1. Gestational Trophoblastic Diseases
DR. SAMAA NAZER
Assistant Professor of Obstetrics & Gynecology
Jeddah, Saudi Arabia

2. Content: Definitions Classifications Etiology of molar pregnancy
Histologic classification
Difference between complete mole and partial mole
Genetic of trophoblastic disease
Diagnosis
Early management care
Follow up
Role of chemotherapy
Malignant variant and its work up and management
Differential diagnosis of bleeding in early pregnancy.

3. DEFINITION
Refers to the spectrum of abnormalities of the trophoblast associated with pregnancy and they specifically secret human chorionic gonadotrophin. They are among the rare human tumours that can be cured even in the presence of wide spread dissemination.

4. GTD include Complete mole Partial hydatidiform mole
Placental site trophoblastic tumour
Choriocarcinoma
Persistent GTT Follow:
Molar pregnancy (common)
Therapeutic or spontaneous abortion
Ectopic pregnancy
Term pregnancy

5. Epidemiology of molar pregnancy
Geographic and racial distribution
There is wide variation in the reported incidence of hydatidiform mole
USA 0.75 to 1.0 per 1000 pregnancy
South East Asia 1.5 to 2.5 times higher
Rate 8 per 1000 pregnancy
Prior hydatidiform mole
The risk increase of subsequent mole by 20 to 40 times
Poor nutrition, low socioeconomic state case control
studies show low dietary intake of carotin, folic acid
Deficiency may contribute the development of mole.
Maternal age
Extreme of age below 20 years or older than 40 years (due to defective fertilization)

6. Complete versus partial hydatidiform mole
Complete mole
a. Pathology
- lack of embryonic or fetal tissue
- chronic villi exhibit genaralized hydrobic swelling .
- diffuse trophoblastic hyperplasia of the syncytiotrophoblast and cytotrophoblast.
2. Genetic.
complete mole only paternal chromosome fertilize an empty egg which result in a chromosome of 46xx in 80% of cases
20% of cases the chromosome is 46 xy
where Haploid sperm one x and one Y fertilized empty egg.
Duplication of the paternal chromosome is called adrogenesis

9. Partial hydatidiform mole
Pathology:
Chorionic villi of varying size .
Foccal hydatidiform swelling, cavitation, and trophoblastic hyperplasia limited to the syncytiotrophoblast.
Marked villous scalloping
Prominent stromal trophoblastic inclusions
Identifiable embryonic fetal tissues.
Genetic of partial mole:
They are usually triploid and have 69 chromosomes of both maternal and
paternal origin (69 xxx) (69 xxy). The most common
mechanism of origin is a haploid egg being fertilized
by two sperm.
Another Mechanism is the abnormal diploid sperm
fertilize the haploid egg

12. Choriocarcinoma
They are malignancies that occur after or in association with pregnancy
Other primary site
Ovary
Testes
Choriocarcinoma occurs in about 3% - 5% of molar pregnancy
The rate in United State is 1 per 20,000 pregnancies
After normal pregnancy 1 per 40,000 term pregnancy
Pathology
Malignant cytotrophoblast and syncytiotrophoblast
Chorionic villi are absent

13. Placental site trophoblastic tumour
It is rare consist of groups of mononucleated and multinucleated trophoblastic cell at the implantation site
Histochemical studies have shown that the cells tend to stain with human placental lactogen (HPL) than for BHCG and both should be monitored.
The treatment is hysterectomy.

14. Clinical features of complete mole
1. Abnormal vaginal bleeding in early pregnancy (97%)
2. Lower abdominal pain
Toxemia before 24 weeks of gestation (27%)
Hyperemesis gravidarum
Uteus large for date (50%)
Hyperthyroidism (7%)
Enlargement of the ovary (Theca lutein ovarian cyst) (20%)
Absent of fetal heart tones and fetal parts.
Expulsion of swollen villi
Trophoblastic embolization (RDs) (2%)

15. Partial Mole
In general patient presents with signs and symptoms of incomplete or missed abortion.
The diagnosis by histologic review of the curettings

16. Prognosis 15% of patient of complete mole → uterine invasion
4% of complete mole → metastasis
4% of partial mole develop persistent tumour
Diagnosis of complete mole:
Ultrasound reliable and sensitive
Finding: a. Absence of the fetus
b. Snow storm – like pattern
c. Ovarian enlargement
B-HCG
The level in normal pregnancy reach peak at weeks rarely exceed level of 100,000 MIU/ML
Level excess of 100,000 MIU/ML suggest GTD

17. Management of molar pregnancy
I – Evaluation of the patient for:
Anemia, hypertension, pulmonary insufficiency,
hyperthyroidism, DIC, by doing:
1. CBC
2. Liver function test (LFT)
3. PT, PTT, fibrinogen
4. Renal function test
5. Thyroid function test (TFT)
6. Blood group Rh
7. Cross match 2 units of blood
8. Chest x-ray
II – Treated by evacuation of the uterus:
Using suction evacuation plus intravenous oxytocin
III – If patient has completed child bearing hysterectomy in high risk patient

18. Follow up The patient should be carefully monitored for the
potential development of malignant sequalae by
serial determination of B-HCG .
The risk of GTT is increased with :
A large uterus
High HCG level
Lutein cyst
History of molar pregnancy
Age above 40 years
HCG follow up is weekly until negative results then monthly up to 1 year and it has to be plotted in a curve.
Pelvic examination every 2 weeks until normal then every 3 months.
Oral contraceptive for 1 year.

20. Diagnosis of Abnormal Follow up
Abnormal regression curve either plateau, or increasing
Symptom of recurrence of patient start to complain of per vaginal bleeding
Management:
To do metastatic work up by:
Pelvic examination
Repeat chest x-ray
B-HCG level
Liver function test
Renal function test
CT scan of chest, abdomen and pelvis
Neurological examination if any abnormality – CT scan of the brain
Chemotherapy

21. Chemotherapy Indication
Plateus or increasing HCG
Metastatic disease is present
Chorio carcinoma is diagnosed in tissue
HCG level is still elevated after 6 months, after evacuation
Abnormal regression curve

22. Gestational trophoblastic Neoplasia
1. ½ cases after molar pregnancy
2. ¼ cases after normal pregnancy
3. ¼ cases after abortion, ectopic pregnancy
FIGO Classification:
Stage I : Confined to the corpus
Stage II : Metastasis outside the uterus to vagina,
or pelvic structure
Stage III : Metastasis on the lungs
Stage IV : Distant metastasis

23. Prognostic classification of GTT
I - Non metastatic GTT
II – Metastatic GTT
a. Good prognosis:
1. Disease present less than 4 month
2. Pre treatment B-HCG less than
40,000 MIU/ml
3. No prior chemotherapy
b. Poor prognosis:
1. Disease present more than 4 months
2. Pre treatment B-HCG greater than 40,000 MIU/ml
3. Presence of metastatic to site other than lungs and
vagina, i.e. liver and brain.
4. Failure of prior chemotherapy

24. Management Nonmetastatic and good prognosis metastatic GTT
Single agent chemotherapy
( Methotrexate )
2. Poor prognosis GTT
Multiple agent chemotherapy
More than one protocol most common is MAC: methotrexate, Actinomycin D, chlorambucil

25. Differential Diagnosis of bleeding in early pregnancy
Abortion (different type)
Ectopic pregnancy
Molar pregnancy
Chorio carcinoma
Blood diseases
Local causes

26. THANK YOU